G-quadruplex-containing oligonucleotides

Abstract

An oligonucleotide molecule has 10 to 50 nucleotides that include at least one G-quartet forming motif having 10 to 20 nucleotide residues. At least 60% of the residues of the G-quartet forming motif are guanosine or deoxyguanosine residues. The oligonucleotide molecule inhibits tumor growth and/or viral or bacterial replication and/or exerts anti-inflammatory effects in mammalian cells.

1 . An oligonucleotide molecule having 10 to 50 nucleotides that form at least one G-quartet forming motif comprising 10 to 20 nucleotide residues, wherein:
 at least 60% of residues of said G-quartet forming motif are guanosine or deoxyguanosine residues, and   the oligonucleotide molecule inhibits tumor growth, and/or inhibits replication of monkeypox, and/or inhibits viral or bacterial replication, and/or exerts anti-inflammatory effects in mammalian cells.   
     
     
         2 . (canceled) 
     
     
         3 . The oligonucleotide molecule according to  claim 1 , wherein >70% of the residues are guanosine or deoxyguanosine residues. 
     
     
         4 . The oligonucleotide molecule according to  claim 1 , wherein the oligonucleotide molecule is synthesized from deoxynucleotides. 
     
     
         5 . The oligonucleotide molecule according to  claim 1 , wherein at least one of the guanosine or deoxyguanosine residues is chemically modified. 
     
     
         6 . The oligonucleotide molecule according to  claim 5 , wherein the chemical modification is a phosphate backbone modification. 
     
     
         7 . The oligonucleotide molecule according to  claim 6 , wherein:
 the phosphate backbone modification comprises thiophosphoryl substitutions selected from phosphorothioate or phosphorodithioate, and   the thiophosphoryl substitutions replace at least 35% of the phosphodiester linkages in the sugar-phosphate backbone of the oligonucleotide molecule.   
     
     
         8 . The oligonucleotide molecule according to  claim 1 , wherein the 10 to 50 nucleotides of the oligonucleotide molecule comprise at least four consecutive triplets of guanosine or deoxy-guanosine residues. 
     
     
         9 . The oligonucleotide molecule according to  claim 1 , wherein the 10 to 50 nucleotides of the oligonucleotide molecule comprise any one of the sequences set forth in SEQ ID NOs. 1 to 4, and/or sequences of SEQ ID NOs 1 to 4 which are truncated by at least 1 nucleotide. 
     
     
         10 . A pharmaceutical composition comprising:
 at least one oligonucleotide molecule according to  claim 1 , and   at least one of a pharmaceutically acceptable excipient, carrier, adjuvant or combination thereof.   
     
     
         11 . A kit comprising at least one oligonucleotide molecule according to  claim 1 . 
     
     
         12 . A method for preventing or treating a tumor, viral or a bacterial infection and/or of inflammation associated therewith in a patient in need thereof comprising administering a therapeutically effective amount of at least one oligonucleotide molecule according to  claim 1  to the patient. 
     
     
         13 . The method according to  claim 12 , wherein the oligonucleotide molecule induces inhibition of tumor growth and/or viral replication in a mammalian cell. 
     
     
         14 . The method according to  claim 13 , wherein the viral infection is caused by a virus selected from the group comprising HS-1 virus, HCN virus, Adenovirus, Zika virus, hepatitis C virus, West Nile virus, influenza virus, RSV virus, Paramyxo-Virus, HIV virus, and coronaviruses. 
     
     
         15 . The method according to  claim 13 , wherein the method treats or prevents a viral infection of the respiratory tract. 
     
     
         16 . The method according to  claim 12 , wherein the treatment of the viral or bacterial disease-associated inflammation and/or tumor growth results from interference with the type I interferon (IFN) and/or the type II IFN pathway or from suppression with interleukin mediated signaling. 
     
     
         17 . The method of  claim 12 , wherein:
 in the oligonucleotide molecule at least one of the guanosine or deoxyguanosine residues is chemically modified,   the chemical modification is a phosphate backbone modification, and   the 10 to 50 nucleotides of the oligonucleotide molecule comprise at least four consecutive triplets of guanosine or deoxyguanosine residues.   
     
     
         18 . The method of  claim 12 , wherein the oligonucleotide molecule is administered in a pharmaceutically acceptable route selected from the group consisting of orally, parenterally, enterally, via the ophthalmic or nasal route, or topically and combinations thereof. 
     
     
         19 . The oligonucleotide molecule according to  claim 1 , wherein:
 >70% of the residues are guanosine or deoxyguanosine residues, and   the oligonucleotide molecule is synthesized from deoxynucleotides.   
     
     
         20 . The oligonucleotide molecule according to  claim 1 , wherein:
 >70% of the residues are guanosine or deoxyguanosine residues, and   the 10 to 50 nucleotides of the oligonucleotide molecule comprise at least four consecutive triplets of guanosine or deoxy-guanosine residues.   
     
     
         21 . The oligonucleotide molecule according to  claim 20 , wherein:
 at least one of the guanosine or deoxyguanosine residues is chemically modified,   the chemical modification is a phosphate backbone modification comprising thiophosphoryl substitutions selected from the group consisting of phosphorothioate or phosphorodithioate, and   the thiophosphoryl substitutions replace at least 35% of the phosphodiester linkages in the sugar-phosphate backbone of the oligonucleotide molecule.